pre-miRNA kuljetus tumasta sytoplasmaan. SMAD4 palautus sytoplasmaan. .

Article in Science 326(5957):1275-9 · November 2009 with 49 Reads 

DOI: 10.1126/science.1178705 ·Nuclear export of microRNAs (miRNAs) by exportin-5 (Exp-5) is an essential step in miRNA biogenesis. Here, we present the 2.9 angstrom structure of the pre-miRNA nuclear export machinery formed by pre-miRNA complexed with Exp-5 and a guanine triphosphate (GTP)-bound form of the small nuclear guanine triphosphatase (GTPase) Ran (RanGTP). The x-ray structure shows that Exp-5:RanGTP recognizes the 2-nucleotide 3' overhang structure and the double-stranded stem of the pre-miRNA. Exp-5:RanGTP shields the pre-miRNA stem from degradation in a baseball mitt-like structure where it is held by broadly distributed weak interactions, whereas a tunnel-like structure of Exp-5 interacts strongly with the 2-nucleotide 3' overhang through hydrogen bonds and ionic interactions. RNA recognition by Exp-5:RanGTP does not depend on RNA sequence, implying that Exp-5:RanGTP can recognize a variety of pre-miRNAs.

Entrez Gene Summary for XPO5 Gene

• This gene encodes a member of the karyopherin family that is required for the transport of small RNAs and double-stranded RNA-binding proteins from the nucleus to the cytoplasm. The encoded protein translocates cargo through the nuclear pore complex in a RanGTP-dependent process. [provided by RefSeq, Aug 2011]
  

GeneCards Summary for XPO5 Gene

XPO5 (Exportin 5) is a Protein Coding gene. Diseases associated with XPO5 include Brain Cancer and Cutaneous Diphtheria. Among its related pathways are Gene Expression and Formation of HIV-1 elongation complex containing HIV-1 Tat. Gene Ontology (GO) annotations related to this gene include binding. An important paralog of this gene is XPO1.

UniProtKB/Swiss-Prot Summary for XPO5 Gene

• Mediates the nuclear export of proteins bearing a double-stranded RNA binding domain (dsRBD) and double-stranded RNAs (cargos). XPO5 in the nucleus binds cooperatively to the RNA and to the GTPase Ran in its active GTP-bound form. Proteins containing dsRBDs can associate with this trimeric complex through the RNA. Docking of this complex to the nuclear pore complex (NPC) is mediated through binding to nucleoporins. Upon transit of a nuclear export complex into the cytoplasm, hydrolysis of Ran-GTP to Ran-GDP (induced by RANBP1 and RANGAP1, respectively) cause disassembly of the complex and release of the cargo from the export receptor. XPO5 then returns to the nuclear compartment by diffusion through the nuclear pore complex, to mediate another round of transport. The directionality of nuclear export is thought to be conferred by an asymmetric distribution of the GTP- and GDP-bound forms of Ran between the cytoplasm and nucleus. Overexpression may in some circumstances enhance RNA-mediated gene silencing (RNAi). Mediates nuclear export of isoform 5 of ADAR/ADAR1 in a RanGTP-dependent manner.
  

  • XPO5_HUMAN,Q9HAV4
• Mediates the nuclear export of micro-RNA precursors, which form short hairpins (PubMed:14681208, PubMed:14631048, PubMed:15613540). Also mediates the nuclear export of synthetic short hairpin RNAs used for RNA interference. In some circumstances can also mediate the nuclear export of deacylated and aminoacylated tRNAs. Specifically recognizes dsRNAs that lack a 5'-overhang in a sequence-independent manner, have only a short 3'-overhang, and that have a double-stranded length of at least 15 base-pairs (PubMed:19965479). Binding is dependent on Ran-GTP (PubMed:19965479).
  

  • XPO5_HUMAN,Q9HAV4
• (Microbial infection) Mediates the nuclear export of adenovirus VA1 dsRNA.
  

  • XPO5_HUMAN,Q9HAV4

Quaternary structure:

• Component of a nuclear export receptor complex composed of XPO5, RAN, dsRNA-binding proteins and dsRNA. Found in a nuclear export complex with XPO5, RAN, EEF1A1, and aminoacylated tRNA. Found in a nuclear export complex with XPO5, RAN, ILF3 and dsRNA. Found in a nuclear export complex with XPO5, RAN and pre-miRNA (PubMed:19965479). Found in a nuclear export complex with XPO5, RAN, ILF3 and minihelix VA1 dsRNA. Found in a nuclear export complex with XPO5, RAN, ILF3, ZNF346 and dsRNA. Interacts with EEF1A1, ILF3, NUP153, NUP214* and ZNF346. Interacts with RAN and cargo proteins in a GTP-dependent manner. Interacts with isoform 5 of ADAR/ADAR1 (via DRBM domains). Interacts with SMAD4; mediates nuclear export of SMAD4 (PubMed:26878725). Interacts with RAN (GTP-bound form) (PubMed:19965479).

*COVID SARS2 nsp9 proteiini tekee interaktion  NUP214